Compiled by Judith Hall, M.D. and William Horton, M.D., Growth, Genetics and Hormones Journal, June 1997. Reproduced with permission from Robert M. Blizzard, M.D., Editor
site The boundary between the 3' end of an intron and the 5' end of
the adjacent exon.
The allelic variation seen among members of the same species.
Phenomenon in which the severity of a genetic condition appears to become more
severe and/or arise at an earlier age with subsequent generations (seen in many
trinucleotide repeat permutations).
The selection of individuals for inclusion in a genetic study (severity, age
of onset, certain features of the trait).
Programmed cell death; a physiologic process conserved to remove unwanted cells.
In a specific population, the occurrence together of 2 or more different phenotypes
more often than expected by chance.
for adenosine triphosphate. The energy-yielding molecule in cells that is used
to drive chemical reactions.
Digestion of the cell's own organelles.
chromosome other than the X or Y. Humans have 22 pairs of autosomal chromosomes.
A disease encoded by a gene on one of the 22 pairs of autosomes.
A trait that is expressed in an individual who is heterozygous for a particular
gene when the mutant allele is on one of the autosomes.
gene A gene that modifies the action of the autosomes.
A trait that is expressed in an individual who is homozygous for a particular
bacterial artificial chromosome.
A genetic crossing of a heterozygous organism and one of its homozygous parents.
chromosome (BAC) Artificial chromosome vector derived from bacteria
used for cloning relatively large DNA fragments.
A rearrangement translocation with no apparent loss or gain of chromosomal material,
resulting in a clinically normal but genetically "abnormal" person.
The differential staining of a chromosome by a variety of techniques that results
in a specific pattern of positively and negatively stained bands for each chromosomal
A substance that can mimic the chemical behavior of 1 of the 4 DNA bases.
base pair substitution
The replacement of 1 base pair by another.
The sex chromatin mass located adjacent to the nuclear membrane in interphase
nuclei, which corresponds to an inactivated X chromosome. One Barr body is seen
in the cells of 46,XX and 47,XXY individuals, and none in the cells of 45,X
and 46,XY individuals.
Mathematical method for calculating probability of the carrier state in mendelian
disorders by combining several independent likelihoods.
The discipline of using computers to address information problems in the life
sciences; it involves the creation of electronic data bases on genomes, protein
pair of homologous chromosomes in association as seen at metaphase of the first
repeats Abbreviation for cytosine-adenine-guanine triplet nucleotide and cytosine-thymine-
guanine triplet nucleotide repeats; they are associated with unstable mutations.
A gene known to be located in the region of interest whose product has biochemical
or other properties suggesting that it may prove to be the disease gene being
candidate gene approach
Strategy to identify disease-associated genes based on finding candidate genes
in a chromosome region in which a disorder is mapped.
cap A modified
nucleotide added to the 5' end of a growing mRNA chain, apparently required
for normal processing, stability, and the translation of mRNA.
The site of initiation of transcription.
Reporter gene assay used to measure activity of a promoter under different conditions,
such as to define elements of a promoter or to study signals that activate an
intact enhancer/promoter. CAT is the abbreviation for the enzyme, chloramphenicol
acetyl transferase, the activity of which is measured in the assay.
A cultured cell type that can be reproduced indefinitely, is, immortalized.
Unmethylated cytosine-guanine sequences that are often found near the 5' ends
of some genes.
mutation A mutation that generates a stop codon, thus preventing further
synthesis of the polypeptide chain.
An abnormality of chromosome number or structure.
That part of medical genetics concerned with health and illness in individuals
Refers here to the production of clinically different phenotypes from mutation
in the same gene.
expression of both alleles in a heterozygous individual, e.g., presence of both
hemoglobin A and S on electrophoresis in an individual heterozygote for sickle-cell
(cDNA) DNA synthesized from an mRNA template, using reverse transcriptase.
analysis A genetic test for determining whether 2 mutations producing
a similar phenotype are allelic.
Presence of the same trait in both members of a pair of twins (or set of individuals).
mosaicism Mosaicism that is seen only in the placenta but not in the
congenic mouse strain
A strain that differs from another in the region containing 1 genetic locus.
Individual seeking, or referred for, genetic counseling.
A series of contiguous, overlapping, cloned DNA fragments.
The number of copies of a transgene integrated into a host genome; used to describe
Reciprocal breaking and rejoining of homologous chromosomes in meiotic prophase
I that results in exchange of chromosomal segments.
of part or a whole chromosome or loss of DNA nucleotide bases.
Refers to an aberrant chromosome that contains 2 centromeres.
The number of chromosomes in most somatic cells, which is double the number
found in the gametes (the haploid number). In humans, the diploid chromosome
number is 46.
A twin pair (or set of individuals) in which one member exhibits a certain trait
and the other does not.
The product of fertilization of 2 separate eggs by 2 separate sperm; nonidentical
A DNA sequence that has been modified to yield a recombinant DNA molecule.
Enzyme that catalyzes religation (reconnection) of 2 fragments of DNA.
Recombination of DNA segments, eg, in cells of the immune system, the variable
(V), diversity (D), and joining (J) regions somatically rearrange to generate
functional antibody genes.
Those conditions that are expressed in heterozygotes, ie, individuals with 1
copy of the mutant gene and 1 copy of the normal allele; refers to phenotype.
An individual with 1 mutant allele at each of 2 different loci.
Guanine-thymidine sequence that defines the splice site at the 5' end of an
The presence of an extra copy of chromosome material. At the gene level, this
refers to the presence of more than 1 copy of a structured gene, usually having
arisen through unequal crossing over. At the chromosomal level, this refers
to an unbalanced state in which there may be a triple dose of a portion of an
autosome, usually occurring as the result of unequal segregation of a translocation
in meiosis (trisomy).
A disorder resulting from the interaction of a common environmental factor with
a specific genetic predisposition, e.g., cigarette smoking causing emphysema
in alpha- antitrypsin deficiency.
Application of a short, high-voltage electric pulse to cells in the presence
of DNA to permit DNA to enter the cells.
Potential method for preimplantation diagnosis of genetic disorders used in
conjunction with in vitro fertilization in which cells are removed and analyzed
at a very early stage in embryonic development.
embryonic stem cells
Cells derived from early embryos that can replicate indefinitely and differentiate
into many cell types. Stem cells serve as a continuous source of new cells;
they may become incorporated into many tissues to produce chimeric animals when
introduced into early embryos, i.e., blastocysts.
Risk of recurrence for multifactorial or polygenic disorders based on family
studies (observed risk).
Enzyme that cleaves bonds between nucleotides of single- or double-stranded
DNA or of RNA at specific sequences of nucleotides.
Encodes capsule or envelope protein of a retrovirus.
A factor that changes the phenotype without changing the genotype.
A plasmid that can exist either independently in the cytoplasm or as an integrated
part of the genome of its bacterial host.
See embryonic stem cells.
expressed sequence tag.
An enzyme that cleaves nucleotide chains at their terminal bonds only.
The degree to which a heritable trait is expressed in an individual. "Variable
expressivity" refers to the variation in phenotype and in severity produced
by the same gene in different individuals.
tag A short fragment of an expressed sequence, cDNA, which serves as
a landmark for gene mapping.
The observable effects of an active gene.
The first generation of animals generated from 2 different inbred strains. These
animals are genetically identical to one another but different from either inbred
The progeny produced from matings between F1 animals. These animals are different
from one another and will contain different mixtures of the genetic variations
that were present in the original inbred progenitors.
A region of a gene preceding or following the transcribed region.
footprinting) Assay used to study DNAbinding proteins.
Refers to animals generated from genetically altered eggs or embryos, is, eggs
microinjected with a transgene.
The high frequency of a mutant gene in a rapidly expanding population founded
by a small ancestral group when 1 or more of the founders were, by chance, carriers
of the mutant gene.
assay An assay used to detect specific protein binding to DNA. Such binding
creates complexes that migrate more slowly during gel electrophoresis than free
DNA. Also known as mobility-shift assay.
A group of genes having similar DNA sequence evolved from a single ancestral
gene. These genes may or may not be located in the same region of a chromosome.
The base triplets that specify the 20 different amino acids.
gene flow Gradual
diffusion of genes from one population to another, as a result of migration
A strategy in which therapeutic genes are introduced into a person's cells to
correct a disease or genetic flaw.
Random fluctuations in gene frequencies, most evident in small populations.
Different mutations causing a similar phenotype; allelic heterogeneity refers
to different mutations at the same locus, whereas locus heterogeneity refers
to mutations at different loci.
A genetic disease that prevents fertility.
Determination of the relative positions of genes on a DNA molecule (chromosome
or plasmid); distances are measured in linkage units, i.e., centimorgans (cM),
A polymorphic genetic property that can be used to distinguish the parental
origin of alleles.
set of closely linked genes that tends to be inherited together as a unit, as
occurs with the A, B. and C loci of the human leukocyte antigen (HLA) gene complex.
for heteroduplex analysis.
Refers to a region of a double-stranded DNA molecule with noncomplementary strands
that originated from different duplex DNA molecules.
A normal morphologic or staining variant of a chromosome.
The existence of more than 1 mitochondrial type in the cells of an individual,
i.e., the presence of both normal and mutant mt DNA in a single individual.
An individual with an abnormal number of chromosomes (as compared to euploid,
which is the normal number of chromosomes).
A molecule consisting of 4 subunits, at least 1 of which differs from the others.
The presence of a single population of mt DNA in the cells of a single individual.
This is normal.
molecule consisting of 4 identical subunits.
A cell formed by fusion of 2 cells of different origin in which the 2 nuclei
have merged into 1. Can be cloned to produce hybrid cell lines.
inbred mouse strain
A strain of mice that has been maintained by successive brother to sister matings
over many generations, e.g., BALB/c and C57BL/6 mice strains.
A molecule that induces the expression of a gene.
A protein that associates with the small subunit of a ribosome when protein
The production of a mutation by insertion of 1 or more copies of a transgene
into a host genome.
in situ Refers
to carrying out experiments or tests with intact tissues.
The untranscribed DNA of unknown function that makes up a large proportion of
the total DNA.
A structural rearrangement of a chromosome in which 2 breaks occur, followed
by the reinsertion of the chromosome segment but in reversed order. It may be
either paracentric, i.e., it does not include the centromere, or pericentric,
i.e., it does include the centromere.
Refers to a biologic or biochemical phenomenon that occurs outside of a living
Refers to a biologic or biochemical phenomenon that occurs within a living organism.
A structural chromosome rearrangement caused by the division of a chromosome
along an axis perpendicular to the usual axis of division; results in chromosomes
with either 2 short arms or 2 long arms.
The presence of 2 identical homologues of a transmitted chromosome from only
1 of the parents. junk DNA with no apparent function.
A structure at the centromere to which the spindle fibers are attached.
lagging strand of
DNA The new strand of a DNA replicating in the 3' to 5' direction.
It is synthesized in short fragments in the 5'to 3' direction that are subsequently
An abnormality of the genome that leads to death in utero, e.g., numerous chromosomal
molecule that can bind to a receptor and thereby induce a signal in the cell,
e.g., a hormone.
A synthetic DNA that carries the recognition site for a restriction enzyme and
that can bind 2 DNA fragments. Also, the stretch of DNA between 2 nucleosomes.
A chromosome map showing the relative positions of genetic markers of a given
species, as determined by linkage analysis; not the same as a physical, or gene,
map, which uses linkage analysis, cytogenetic examination, and physical techniques
to generate the map.
The arrangement of alleles of linked loci on chromosomes.
loss of heterozygosity
Describes a locus (or loci) at which a deletion or other process has converted
the locus from heterozygosity to homozygosity or hemizygosity. Phenomenon can
lead to cancers by loss of tumor suppressor genes.
lyonization A term used for the phenomenon of X inactivation, which was first proposed by the geneticist Mary Lyon.
A method for determining the exact nucleotide sequence via a chemical degradation
A trait obeying Mendel's first law of independent segregation of the alleles
at the same locus conveyed by each parent.
The minimal elements of a promoter, including the TATA box and transcription
initiation site, which is inactive unless regulatory elements that enhance promoter
activity are placed upstream; used to test candidate sequences for enhancer
The presence in 1 chain of double-stranded DNA of a base that is not complementary
to the corresponding base in the other chain. Also known as mispairing.
A small, intracellular, spherical to rod-shaped cytoplasmic organelle, enclosed
by Z membranous spaces; the inner membrane is folded, forming a series of projections
called cristae. Mitochondria are the principal sites of ATP synthesis; they
contain enzymes of the tricarboxylic acid cycle and enzymes for fatty acid oxidation,
oxidative phosphorylation, and many other biochemical pathways. They contain
their own nucleic acids and ribosomes, replicate independently, and code for
the synthesis of some of their own proteins.
The ability of a single-stranded DNA or RNA to anneal to its complementary single
strand by Watson-Crick base pairing.
DNA sequences that are capable of inserting themselves into other locations
in the genome.
An assay used to detect specific protein binding to DNA. Such binding creates
complexes that migrate more slowly during gel electrophoresis than free DNA.
Also known as gel-shift assay.
A gene that alters the expression of a gene at another locus.
The study of the structure and function of genes at the molecular level.
A group of cells that consist of a single clone, i.e., all cells are derived
from the same single ancestral cell.
Describing a single gene or mendelian trait.
protein present in embryonic tissues in a concentration gradient that induces
a developmental process.
An individual or tissue with at least 2 cell lines differing in genotype or
karyotype, derived from a single zygote.
An aneuploid condition in which a specific chromosome is present in only single
copy, giving the individual a total of 45 chromosomes.
to twins derived from a single fertilized egg.
A type of genetic mapping in which the recombination frequencies among 3 or
more loci are estimated simultaneously.
Relating to mice or rats.
substance that causes a mutation.
The protein product of the neurofibromatosis type 1 gene.
An alteration in DNA sequence that appears for the first time in a family as
the result of a mutation in 1 of the parent's germ cell.
nondisjunction The failure
of homologous chromosomes (in mitosis or meiosis 1) or sister chromatics (in
meiosis 11) to separate properly into different progeny cells.
Lack of clinical expression of the mutant phenotype in an individual with the
A pair of biologic parents and their children.
Immunologically deficient mice used to permit growth of tumor cells from mouse
and other species, such as human.
An allele that results in either the absence of the gene product or the absence
of any function at the phenotypic level.
An individual who is clinically unaffected but, on the basis of pedigree analysis,
must carry a particular mutant allele.
Diseases or traits that result from the effects of relatively few genes, some
of which have rather large effects.
A short DNA probe whose hybridization is sensitive to a single base mismatch.
genes of vertebrates that are involved in control of cell growth and have been
preserved throughout evolution. When mutated, overexpressed, or amplified in
somatic cells, oncogenes may cause neoplastic transformation.
Membrane-bound intracellular, cytoplasmic structures having specialized functions,
e.g., mitochondria, plastics, Golgi apparatus, lysosomes.
origin of replication
(ORI) The site where DNA replication starts.
outbred mouse strains
Strains of mice propagated by nonstandardized matings. These mice retain substantial
artificial chromosome vector derived from the temperate bacteriophage, P1, used
for cloning 100- to 200-kb DNA fragments.
In molecular biology, a nucleotide sequence in which the 5'to 3' sequence of
1 strand of a segment of DNA is the same as that of its complementary strand.
The sites of many restriction enzymes are palindromes.
for primer extension preamplification.
The chromatographic pattern of peptides obtained after partial hydrolysis of
a protein or peptide. The technique also may be applied to DNA and RNA.
Enzymes localized to the peroxisomes. These enzymes are initially synthesized
by the free polyribosomes and then enter the cytoplasm and eventually are localized
to the peroxisomes. There are at least 40 enzymes. Some are involved in the
production and decomposition of hydrogen peroxide and some are concerned with
lipid and amino acid metabolism.
A subcellular organelle surrounded by a single membrane containing at least
40 enzymes involved in energy production.
The determination of the linear positions of genes on a DNA molecule; distances
are measured in physical units, i.e., base pairs, kilobases, and megabases.
Lectin isolated from the red bean used to agglutinate red blood cells and stimulate
lymphocytes to divide; used in preparation of peripheral blood karyotypes.
growth factor (PDGF) A protein, produced by platelets and other cells,
that strongly stimulates cell growth and division and is involved in normal
wound healing. The gene for PDGF is identical to the proto-oncogene sis.
pulsed field electrophoresis
An electrophoretic technique that allows the separation of relatively long (>5,000
kb) sequences of DNA.
A mutation in a single nucleotide.
The addition of approximately 200 adenosine residues at the 3' end of messenger
RNAs, apparently involved in their transport of the nucleus and stability.
Enzymes that catalyze the combining of nucleotides to form RNA or DNA (genetic
transcription and DNA replication).
Structures composed of multiple ribosomes attached to mRNA in the process of
Either of the 2 haploid gamete nuclei just prior to their fusion in the fertilized
ovum. Transgenic lines are often generated by microinjection of the transgene
into the pronuclear region of these haploid gametes.
The correction of errors in the nucleotide sequence that can occur during replication,
transcription, or translation.
mechanism In dominant disorders, 1 mutant subunit leads to the loss
of function of an entire multimeric protein, e.g., collagen.
Normal genes that are found in normal eukaryotic cells concerned with various
aspects of cell division. If amplified, mutated, rearranged, or picked up by
a retrovirus, they may give rise to oncogenes that can cause cancer.
region The distal tip of the Y chromosome short arm, which undergoes
crossover with the distal tip of the X chromosome short arm during meiosis in
The pattern of inheritance produced by the mating of an affected homozygote
with an individual heterozygous for the same recessive trait so that homozygous
affected members appear in 2 or more successive generations.
Q-banding The pattern of bright and dim fluorescent crossbands seen on chromosomes under ultraviolet light after quinacrine mustard staining.
A chromosome banding technique in which chromosomes are heated in a phosphate
buffer; produces dark and light bands in patterns that are the reverse of those
produced by G-banding.
A transmembrane or intracellular protein involved in transmission of a cell
A chromosome in an offspring that has a genotype not found in either parent,
due to crossing over in meiosis.
In linkage analysis, the fraction of meiotic events that show a recombination
between 2 loci.
A gene coding for a protein that regulates other genes.
The identical duplication of DNA.
The unwound region of the DNA double helix in which replication takes place.
Refers to changes in the proportions of mitochondrial DNA alleles as the mitochondria
A gene used to analyze another gene.
The process in which DNA is exposed to restriction enzymes (restriction endonuclease),
causing it to be cleaved into fragments of DNA called restriction fragments.
A map of a DNA sequence with restriction enzyme recognition sites serving as
A short sequence in DNA that can be recognized and cut by a specific restriction
The application of human gene mapping to clone the gene responsible for a particular
disease when no information about the biochemical basis of the disease is available.
Cytoplasmic organelles composed of ribosomal RNA and protein, on which polypeptide
synthesis from messenger RNA occurs.
A structurally abnormal chromosome in which the end of each chromosome arm has
been deleted and the broken arms have reunited to form a ring.
Abbreviation for reverse transcriptase polymerase chain reaction.
The enzymatic method for determining the exact nucleotide sequence of a cloned
fragment of DNA.
A portion of the DNA that differs enough in base composition so that it forms
a distinct band on cesium chloride gradient centrifugation; usually contains
highly repetitive DNA sequences.
nuclear structure observed when histones are experimentally removed from chromosomes.
Thought to represent a structural component of the nucleus and of chromosome.
The separation of allelic genes at meiosis. Because allelic genes occupy the
same locus on homologous chromosomes, they pass to different gametes.
site (STS) A short fragment of DNA whose exact sequence is found nowhere
else in the genome; typically about 200 to 300 bp. Polymerase chain reaction
can be used to amplify the known sequences, which can serve as physical landmarks
The group comprising all the siblings (brothers and sisters) in a family.
A mutant gene that has no detectable phenotypic effect.
The cis regulatory element that reduces transcription of a gene.
The process of creating mutations at specific locations, in contrast to naturally
occurring random mutations.
A nonrandom pattern of inactivation of 1 of the X chromosomes in a female that
can arise through a variety of mechanisms. When this occurs, the active X chromosome
may bear the mutant allele and the female will show signs and symptoms of the
disease. The female is called a manifesting heterozygote or a carrier.
somatic cell gene
therapy The insertion of new DNA material into a particular tissue
of an affected individual in such a way that the inserted DNA does not enter
for single-strand conformation polymorphism.
for sequence-specific primer. These are used in PCR reactions.
for short tandem repeat. These often serve as polymorphic markers.
for short tandem repeat polymorphism.
Refers to genetically identical members of the same species.
A genetic map in which expressed sequences, e.g., mRNAs, mRNA transcripts, corresponding
to genes are mapped; a functional blueprint of the genome.
A retrovirus carrying an additional DNA sequence (often an oncogene) that confers
the ability to transform infected cells to malignant phenotype.
foreign gene; typically, a gene produced by recombinant DNA techniques.
A DNA sequence that can move from one chromosomal location to another.
A mutation in which purine is substituted for pyrimidine or vice versa.
A sequence of 3 nucleotides comprising a codon of a nucleic acid and representing
the code for an amino acid (triplet code, codon).
gene A gene thought to suppress formation of tumors; loss of suppression
leads to malignant transformation. P53 is an example of a tumor-suppresser gene.
over Crossing over between similar DNA sequences that are misaligned,
resulting in sequences with deletion or duplication of DNA segments. A cause
of a number of genetic variants, e.g., -thalassemia and Lepore hemoglobin.
Refers to the variable severity of a genetic trait. Individuals with the same
mutant gene with pleiotropic effects frequently show variable expressivity due
to either environmental effects or effects of other genes modifying the expression
of the mutant gene.
The term used to indicate the normal allele (often symbolized as +) or the normal
The reciprocal translocation between the X chromosome and 1 of the autosomes.
A trait that is manifested in the heterozygous female as well as in the male
who has the mutant allele on 1 of the X chromosomes.
A disorder manifested exclusively in a male who is a heterozygote or a homozygous
female when the abnormal gene is carried on the X chromosome. A female is usually
a carrier if she is heterozygous and transmits the disease to the son.
zinc finger proteins
Transcription-activator proteins containing finger-like structures containing
A Southern blot containing conserved DNA sequences from related genes of different
species. It is taken as evidence that the sequences are coding sequences from
a specific gene.
Scharpf R. TBASE Glossary:
The Transgenic/Targeted Mutation Database. Baltimore, Md: Johns Hopkins
University School of Medicine (http://www.gdb.org/Dan/tbase/docs/glossary.html).
Bradley J. Johnsen D, Rubenstein
D. Molecular Medicine. Oxford, England: Blackwell Science; 1995.
Thompson MW, McInnes RR,
Willard HF. Genetics in Medicine. 5th ed. Philadelphia, Pa: WB Saunders;1991.
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